Using a new technique known as lesion network mapping, Harvard Medical School researchers at Brigham and Women’s Hospital have mapped addiction remission to entire brain circuits rather than specific brain regions, pointing to new targets for treatment. Their results are published in Nature Medicine.
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In the United States, substance use disorders are a leading cause of death among young people. Treatments such as deep brain stimulation hold promise for helping people overcome addiction, but many questions remain about which brain areas should be targeted.
The new work contributes to growing knowledge gained from patients no longer addicted to nicotine after experiencing a brain lesion, such as a stroke.
“By looking beyond individual brain regions and, instead, at the brain circuit, we have found targets for addiction remission and are eager to test them through clinical trials rigorously,” said Michael D. Fox, HMS associate professor of neurology at Brigham and Women's.
“Ultimately, our goal is to take larger steps towards improving existing therapies for addiction and open the door for remission,” he said.
Neuromodulation therapies, such as deep brain stimulation, transcranial magnetic stimulation, and MRI-guided focused ultrasound, allow clinicians to directly target brain circuits and improve symptoms in ways that may not be possible through treatment with medication. But knowing the location to target is critical.
In a previous study, researchers used lesion network mapping to examine patients whose essential tremors resolved, confirming targets used in treatment with deep brain stimulation. The study authors set out to apply the same approach to addiction remission.
“Although we know much about the neurobiological mechanisms in addiction, treatment options are still very limited. Our findings with essential tremor made us realize the potential of this approach to localize key brain circuits mediating symptom improvement,” said Juho Joutsa of the Turku Brain and Mind Center and Clinical Neurosciences at the University of Turku.
Fox and colleagues used data from two independent cohorts of patients with an addiction to nicotine who then suffered a brain lesion, usually from a stroke.
Comparing lesions
Fox’s team compared lesions in patients unable to quit smoking to lesions resulting in remission of smoking addiction. They then used a database known as the human connectome to map each lesion to the larger brain circuit.
They found that the two smoking lesion datasets that led to remission of smoking addiction mapped to a specific brain circuit.
To their surprise, they also discovered in a third alcoholism lesion dataset that a reduced risk of alcoholism mapped to a similar brain circuit, suggesting a potential therapeutic, targetable neural pathway for addiction in general rather than addiction to a specific substance.
“Although neuromodulation treatments using electricity or brain lesions have shown promise in relieving substance addiction, the therapeutic target has been unclear,” said Fox.
“Now that our study has identified a target—a specific human brain circuit—we hope to test whether targeted neuromodulation to this brain circuit provides sustainable symptom relief to our patients,” he said.
The authors acknowledge two primary study limitations. First, the results are solely based on retrospective analysis of existing datasets, and second, the datasets examined covered only specific substances of abuse.
The researchers, therefore, advocate for prospective validation of their findings through clinical trial testing and an examination of additional substances of addiction to determine whether their findings can be applied widely.
“We were excited to discover that our mapped lesions associated with addiction remission led back to a common brain circuit. While our findings point towards therapeutic targets for addiction, we need to test these targets in randomized clinical trials,” said Fox.
“We study brain lesions in the context of the brain circuit because it provides a powerful way to understand the causal links between addiction and our neuroanatomy. We hope we can make significant strides towards helping patients with substance use disorders,” he added.
Source: HMS